The PCILO Method

The syn-anti conformational problem of a- and /3-pyrazofurins (756 one of the rare naturally occurring pyrazole compounds, see Section 4.04.4.4.3), which involves a rotation around a pyrazolic sp carbon atom and a sugar sp carbon atom, has been studied theoretically using the PCILO method (81MI40403). In agreement with the experimental observations, the /3 anomer is energetically more favourable than the a anomer, the preferred conformations being anti and syn, respectively. 

The PCILO method has been applied237,238 to calculate the dipole moments of several conformers of uridine and deoxyuridine (see footnote a to Table XXII). However, at present, it is difficult to make a detailed comparison of the calculated dipole moments of nucleosides with the experimental data. In solution, the nucleosides exist as a mixture of several conformers in unknown proportions. 

An early example implementing the general approach to take into account first the intrabond correlation, is presented by the PCILO - perturbational configuration interaction of localized orbitals method [121,122], As one of its authors, J.-P. Malrieu mentions in [122], the PCILO method opposes the majority of the QC methods in all the fundamental concepts. In contrast to the majority of the methods based on the variational principle, the PCILO method is based on estimating the energy by perturbation theory. Also, the majority of the QC methods use one-electron HFR approximation, at least as an intermediate construct, whereas the PCILO is claimed to addresses directly the V-electron wave function and takes into account all surviving matrix elements of the electron-electron interactions. In contrast with other QC... 

All these statements, although correct in principle, are not precise from the technical point of view. For example, the zero approximate wave function in the PCILO method is a one-electron approximate function constructed from the bond wave functions determined by an a posteriori localization procedure from an HFR function. Thus the bond orbitals appear after a unitary transformation of the canonical MOs, which correspond to some more or less arbitrary localization criteria [123-125]. 

J.-P. Malrieu. The PCILO method, in Semiempirical Methods of Electronic Structure Calculation. Part A Techniques, ed. by G.A. Segal, Plenum, New York, 1977. 

The PCILO method has been extensively applied to conformational questions in biochemistry, mainly by Pullman and co-workers. This general field has been the subject of recent reviews.158 159 In only a few years a vast literature of such calculations has appeared. The following list of examples should, however, allow access to... 

Dipole moment of cytidine as a function of rotation about the glycosidic bond has been calculated by the ZNDO method by Kang (for the different puckerings of the sugar, o<4 )-o(5 ) = 300°) and by the PCILO method by WeUer-Feilchenfeld et td. (for... 

The evaluation of the dipole moment of uridine as a function of the rotation about the glycosidic bond has been carried out by the PCILO method by Weiler-Feilchenfeld et (for the C -endo gg and C -endo gg conformations). The same method has heen used by Berthod and Pullman to calculate the dipole moments of anti and syn conformers of uridine, Cg-endo gg (7.0 and 3.4 D, respectively) and those of deoxyuridine, Ca-endo gg (4.8 and 4.8 D, respectively). For the n--contributions for the dipole moments of uracils see refs. 174,177,407. 

Ab initio SCF energy calculations were used to determine the structures of several carbohydrates [46-47]. The PCILO method [48] was applied to carbohydrates [49]. The X-a method [50] can be parametrized for metal atoms so that calculations on sugar-metal complexes are possible (for example, the studies on sugar-metal interactions by Tajmir-Riahi [51]). 

Table III gives the energy of the optimized n -tr complexes obtained frgm the empirical energy program at optimum values of R = 3.2A. We see from this table that interaction energies for XmP are comparable to those obtained by the PCTLO method at 3.2l. For AMS complexes, the empirical method yields somewhat larger energies than those obtained at 3.2A with the PCILO method.

With the exception of the cyclopropylmetbane, the main discrepancy is the relatively large energy calculated for the 2,3 - dimethylfuran. The stabilization energies of the AMS complexes calculated by the empirical method correlate more with the measured affinities and antagonist potencies than those for the AMP complexes. Additionally, more stable complexes with AMS are found by the empirical method than by the PCILO method. Taken together, the results of both methods indicate that either the phosphate or sulfate anion is a reasonable model for the anionic opiate receptor site. 

In the case of the valyl residue PCILO predicts a global minimum where our method predicts a maximum. As seen in Figure 11 the conformation of the valyl residue in globular proteins occupies the minimum regions located by CONFOR and what would be a local minima in the PCILO method. The barrier between = 270,... 

In connection with these earlier quantum chemical studies we had also extended the derivations of some of the semi-rigorous techniques [such as deriving the necessary expressions for including d orbitals in the INDO method (25)1 suggested procedures to improve other methods [how to improve the description of lone pairs in the PCILO method (26)1 and performed calculations by various techniques comparing the results of less rigorous calculations with our large basis set ab-initio calculations (27 >28). 

In the preceding examples on the application of quantum-mechanical methods to the study of conformational problems in biochemistry, we have centered our attention essentially on results obtained by the PCILO method. The reason for this situation resides in the first place in the fact that the results obtained by this procedure are by far the most abundant. A second reason is, however, that they appear also the most satisfactory, being in particular superior to those obtained by the Extended Huckel Theory, which comes next after PCILO in the amount of work carried out. (For practical reasons, very few calculations have been performed in this field using the CNDO/2 method.)... 

One of the immediate successes of the PCILO method when applied to the simple model dipeptides, say, glycyl-L-alanine, was to predict the most stable form of such a compound, a conformation which completely escaped the attention of the great majority of the previous empirical computations and also of the EHT calculations. This conformation is represented by a seven-membered hydrogen-bonded ring (Fig. 28). As the next most stable conforma-... 

Recently a systematic investigation of the conformational and electronic aspects of pharmacology has been launched in our laboratory, using the PCILO method. The compounds investigated for which results are already available are those which have been previously investigated by the EHT method acetylcholine, nicotine and muscarine 84>, serotonine 85 histamine 86), ephedrine, norephedrine and dopamine 87>, but also others tyramine, noradrenaline, ephedrine, amphetamine and privine 87), a number of barbiturates 88 and a number... 

Fig. 18.—Torsional Potential of the Exocyclic C-O Bond in the Axial Form of 2-Methox-yoxane Calculated by the PCILO Method (Full Line) and Corresponding Potential in Dimeth-oxymethane (Dashed Line) Calculated by the CNDO/2 Method (Curve a) and by the ab initio Method (Curve b). ...

It is also worth mentioning an alternative approach [77] to describe the localized character of njr excitations. It based on the PCILO (Perturbative Configuration Interaction using Localized Orbitals) method where Cl calculations are carried out in a basis of locally excited determinants. Accordingly, the local structure of nn — excitations is detected by the weights of the appropriate determinant. At the same time, our approach includes no localization procedure for MOs, and excited state local properties arise directly from the main indices (14.35), (14.37), and (14.38). Moreover, the PCILO method is somewhat outdated at least its extension to the DPT methodology seems not reasonable. We cite work [77] as the first paper where the localization phenomena otnn — transitions were discussed from a quantum-chemical viewpoint. 

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